2J0M

Crystal structure a two-chain complex between the FERM and kinase domains of focal adhesion kinase.

Summary for 2J0M

• Entry DOI: 10.2210/pdb2j0m/pdb
• Related: 1KTM 1PV3 1QVX 2AEH 2AL6 2J0J 2J0K 2J0L
• Descriptor: FOCAL ADHESION KINASE 1, 1,2,3,4-TETRAHYDROGEN-STAUROSPORINE, ... (4 entities in total)
• Functional Keywords: focal adhesion, cell migration, phosphorylation, ferm, kinase, transferase, atp-binding, integrin signaling, nucleotide-binding, tyrosine-protein kinase
• Biological source: GALLUS GALLUS (CHICKEN); More
• Total number of polymer chains: 2
• Total formula weight: 74673.56

Authors

Lietha, D.,Cai, X.,Li, Y.,Schaller, M.D.,Eck, M.J. (deposition date: 2006-08-03, release date: 2007-07-03, Last modification date: 2023-12-13)

Primary citation

Lietha, D.,Cai, X.,Li, Y.,Schaller, M.D.,Eck, M.J.
Structural Basis for the Autoinhibition of Focal Adhesion Kinase.
Cell(Cambridge,Mass.), 129:1177-, 2007

PubMed Abstract: Appropriate tyrosine kinase signaling depends on coordinated sequential coupling of protein-protein interactions with catalytic activation. Focal adhesion kinase (FAK) integrates signals from integrin and growth factor receptors to regulate cellular responses including cell adhesion, migration, and survival. Here, we describe crystal structures representing both autoinhibited and active states of FAK. The inactive structure reveals a mechanism of inhibition in which the N-terminal FERM domain directly binds the kinase domain, blocking access to the catalytic cleft and protecting the FAK activation loop from Src phosphorylation. Additionally, the FERM domain sequesters the Tyr397 autophosphorylation and Src recruitment site, which lies in the linker connecting the FERM and kinase domains. The active phosphorylated FAK kinase adopts a conformation that is immune to FERM inhibition. Our biochemical and structural analysis shows how the architecture of autoinhibited FAK orchestrates an activation sequence of FERM domain displacement, linker autophosphorylation, Src recruitment, and full catalytic activation.

PubMed: 17574028
DOI: 10.1016/J.CELL.2007.05.041

Experimental method

X-RAY DIFFRACTION (2.8 Å)